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CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases

  • Nicholas B. Figura
  • Thrisha K. Potluri
  • Homan Mohammadi
  • Daniel E. Oliver
  • John A. Arrington
  • Timothy J. Robinson
  • Arnold B. Etame
  • Nam D. Tran
  • James K. Liu
  • Hatem Soliman
  • Peter A. Forsyth
  • Solmaz Sahebjam
  • H. Michael Yu
  • Hyo S. Han
  • Kamran A. AhmedEmail author
Clinical Study

Abstract

Purpose

Cyclin-dependent kinase (CDK) 4/6 inhibitors are becoming increasingly utilized in the setting of advanced, hormone receptor (HR+) positive breast cancer. Pre-clinical data suggests a potential synergy between radiation therapy (RT) and CDK4/6 inhibitors. We assessed clinical outcomes of patients treated at our institution with the use of CDK4/6 inhibitors and stereotactic radiation in the management of HR+ breast brain metastases.

Methods

A retrospective analysis of patients who received stereotactic radiotherapy for HR+ brain metastases within 6 months of CDK4/6 inhibitor administration was performed. The primary endpoint was neurotoxicity during or after stereotactic radiation. Secondary endpoints were local brain control, distant brain control, and overall survival (OS).

Results

A total of 42 lesions treated with stereotactic radiation in 15 patients were identified. Patients received either palbociclib (n = 10; 67%) or abemaciclib (n = 5; 33%). RT was delivered concurrently, before, or after CDK4/6 inhibitors in 18 (43%), 9 (21%), and 15 (36%) lesions, respectively. Median follow-up following stereotactic radiation was 9 months. Two lesions (5%) developed radionecrosis, both of which received four prior RT courses to the affected lesion prior to onset of radionecrosis and subsequently managed with steroids and bevacizumab. Six- and 12-month local control of treated lesions was 88% and 88%, while 6- and 12-month distant brain control was 61% and 39%, respectively. Median OS was 36.7 months from the date of brain metastases diagnosis.

Conclusions

Stereotactic radiation to breast brain metastases was well tolerated alongside CDK4/6 inhibitors. Compared to historical data, brain metastases control rates are similar whereas survival appears prolonged.

Keywords

CDK4/6 inhibitors Abemaciclib Palbociclib Breast cancer Brain metastases Stereotactic radiotherapy 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest

Hyo S. Han declares that she has received a speaker’s honorarium from Lilly Pharmaceuticals; Peter A. Forsyth has received research funding and is on the advisory board for Pfizer.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (University of South Florida Institutional Review Board Pro00023399) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nicholas B. Figura
    • 1
  • Thrisha K. Potluri
    • 1
  • Homan Mohammadi
    • 1
  • Daniel E. Oliver
    • 1
  • John A. Arrington
    • 2
  • Timothy J. Robinson
    • 1
  • Arnold B. Etame
    • 3
  • Nam D. Tran
    • 3
  • James K. Liu
    • 3
  • Hatem Soliman
    • 4
  • Peter A. Forsyth
    • 3
  • Solmaz Sahebjam
    • 3
  • H. Michael Yu
    • 1
  • Hyo S. Han
    • 4
  • Kamran A. Ahmed
    • 1
    Email author
  1. 1.Department of Radiation OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Department of RadiologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  3. 3.Department of Neuro OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  4. 4.Department of Breast OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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